A Phase 2 Open-Label, Multicenter Study Evaluating The Safety And Efficacy of Axicabtagene Ciloleucel Concomitant With Prophylactic Steroids In Subjects With Relapsed Or Refractory Large B-Cell Lymphoma In The Outpatient Setting
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 35
- 试验地点
- 32
- 主要终点
- Percentage and Severity of Participants with Treatment-emergent Cytokine Release Syndrome (CRS) and Neurologic Events
研究概览
简要总结
The goal of this clinical study is to learn more about the study drug, axicabtagene ciloleucel, in participants with relapsed or refractory large B-cell lymphoma (LBCL) in the outpatient setting.
详细描述
Participants who complete at minimum 24 months follow up will be transitioned to a separate long-term follow-up study (study KT-US-982-5968) to complete the remainder of the 15-year follow-up assessments.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed large B-cell lymphoma (LBCL), including the following types defined by World Health Organization (WHO) 2016 classification, by local pathology laboratory assessment, are eligible as defined below:
- •Diffuse large B-cell lymphoma (DLBCL) not otherwise specified.
- •High-grade B-cell lymphoma (HGBL) with or without MYC and BCL2 and/or BCL6 rearrangement.
- •DLBCL associated with chronic inflammation; Epstein-Barr virus (EBV) + DLBCL.
- •Primary mediastinal (thymic) LBCL.
- •Primary cutaneous DLBCL, leg type.
- •Transformation of follicular lymphoma to DLBCL will also be included.
- •Relapsed or refractory disease after 1 or more lines of therapy.
- •Individuals must have received adequate prior therapy including:
- •Anti-CD20 monoclonal antibody AND
- •An anthracycline-containing chemotherapy regimen.
- •At least 1 measurable lesion according to the Lugano Response Criteria for Malignant Lymphoma. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Individual agrees to outpatient treatment setting and to adhere to the prespecified clinical monitoring requirements.
排除标准
- •History of autologous or allogeneic stem cell transplant.
- •Prior cluster of differentiation (CD)19 targeted therapy.
- •Prior chimeric antigen receptor therapy or other genetically modified T-cell therapy.
- •Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous (IV) antimicrobials for management. Simple urinary tract infection and uncomplicated bacterial pharyngitis are permitted if responding to active treatment and after consultation with the Kite medical monitor.
- •Individuals with detectable cerebrospinal fluid malignant cells, brain metastases, or with a history of central nervous system (CNS) lymphoma or primary CNS lymphoma. DLBCL epidural involvement should be considered as positive CNS disease.
- •In the investigator's judgment, the individual is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Axicabtagene Ciloleucel
Participant will receive lymphodepleting chemotherapy (cyclophosphamide 500 mg/m^2/day and fludarabine 30 mg/m^2/day) over 3 days (Days -5, -4, and -3) followed by prophylactic corticosteroid treatment with 10 mg dexamethasone on Day 0 (prior to axicabtagene ciloleucel), Day 1, and Day 2.
Participant will receive axicabtagene ciloleucel consisting of a single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells on Day 0 (following dexamethasone 10 mg) at a target dose of 2 x 10^6 cells/kg.
干预措施: Axicabtagene Ciloleucel (Biological)
Axicabtagene Ciloleucel
Participant will receive lymphodepleting chemotherapy (cyclophosphamide 500 mg/m^2/day and fludarabine 30 mg/m^2/day) over 3 days (Days -5, -4, and -3) followed by prophylactic corticosteroid treatment with 10 mg dexamethasone on Day 0 (prior to axicabtagene ciloleucel), Day 1, and Day 2.
Participant will receive axicabtagene ciloleucel consisting of a single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells on Day 0 (following dexamethasone 10 mg) at a target dose of 2 x 10^6 cells/kg.
干预措施: Cyclophosphamide (Drug)
Axicabtagene Ciloleucel
Participant will receive lymphodepleting chemotherapy (cyclophosphamide 500 mg/m^2/day and fludarabine 30 mg/m^2/day) over 3 days (Days -5, -4, and -3) followed by prophylactic corticosteroid treatment with 10 mg dexamethasone on Day 0 (prior to axicabtagene ciloleucel), Day 1, and Day 2.
Participant will receive axicabtagene ciloleucel consisting of a single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells on Day 0 (following dexamethasone 10 mg) at a target dose of 2 x 10^6 cells/kg.
干预措施: Fludarabine (Drug)
Axicabtagene Ciloleucel
Participant will receive lymphodepleting chemotherapy (cyclophosphamide 500 mg/m^2/day and fludarabine 30 mg/m^2/day) over 3 days (Days -5, -4, and -3) followed by prophylactic corticosteroid treatment with 10 mg dexamethasone on Day 0 (prior to axicabtagene ciloleucel), Day 1, and Day 2.
Participant will receive axicabtagene ciloleucel consisting of a single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells on Day 0 (following dexamethasone 10 mg) at a target dose of 2 x 10^6 cells/kg.
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Percentage and Severity of Participants with Treatment-emergent Cytokine Release Syndrome (CRS) and Neurologic Events
时间窗: Up to 24 months
次要结局
- Rates of Hospitalization After Axicabtagene Ciloleucel Infusion as Measured by Proportion of Hospitalized Participants Within 7 days(First infusion date of axicabtagene ciloleucel up to 7 days)
- Rates of Hospitalization After Axicabtagene Ciloleucel Infusion as Measured by Proportion of Hospitalized Participants Within 14 days(First infusion date of axicabtagene ciloleucel up to 14 days)
- Rates of Hospitalization After Axicabtagene ciloleucel Infusion as Measured by Proportion of Hospitalized Participants Within 30 days(First infusion date of axicabtagene ciloleucel up to 30 days)
- Proportion of Intensive Care Unit (ICU) Admitted Participants(Up to 24 months)
- Percentage of Participants Experiencing Treatment- Emergent Serious Adverse Events(First infusion date of axicabtagene ciloleucel up to 24 months)
- Change in the European Quality of Life Five Dimensions Five Levels Scale (EQ-5D-5L) From Baseline to Month 6(Baseline, 6 Months)
- Overall Survival (OS)(Up to 24 months)
- Rates of Hospitalization After Axicabtagene Ciloleucel Infusion as Measured by Proportion of Hospitalized Participants 3 Days After Infusion Date(First infusion date of axicabtagene ciloleucel up to 3 days)
- Duration of Initial Hospitalization After Axicabtagene Ciloleucel Infusion(First infusion date of axicabtagene ciloleucel up to 24 months)
- Duration of ICU Admission During First Hospitalization After Axicabtagene Ciloleucel Infusion(Up to 24 months)
- Percentage of Participants Experiencing Treatment- Emergent Adverse Events(First infusion date of axicabtagene ciloleucel up to 24 months)
- Complete Response (CR) Rate as Assessed by Investigator Assessment(Up to 24 months)
- Duration of response (DOR) as Assessed by Investigator Assessment(Up to 24 months)
- Progression-free Survival (PFS) as Assessed by Investigator Assessment(Up to 24 months)
- Peak Serum Levels of Chemokines: IL-8, C-X-C Motif Chemokine Ligand-10 (CXCL-10), and Monocyte Chemotactic Protein-1 (MCP-1)(Up to 24 months)
- Objective Response Rate (ORR) as Assessed by Investigator Assessment(Up to 24 months)
- Peak Serum Levels of Inflammatory and Immune Modulating Cytokines: IFN-γ, IL-1, IL-6, IL- 13, IL-17, IL-1, IL-1RA, Granulocyte-macrophage Colony Stimulating Factor (GM-CSF), Tumor Necrosis Factor-Alpha (TNF-α), and IL-12p40/p70(Up to 24 months)
- Peak Serum Levels of the Acute Phase Response Proteins: C-Reactive Protein (CRP), Serum Amyloid A (SAA), Soluble IL-2 Receptor Alpha (sIL-1Ra), Ferritin(Up to 24 months)
- Blood Levels of Axicabtagene Ciloleucel Chimeric Antigen Receptor (CAR) T-cells Over Time(Up to 24 months)
- Time to Onset of CRS and Neurologic Events Following Axicabtagene Ciloleucel Administration(First infusion date of axicabtagene ciloleucel up to 24 months)
- Duration of CRS and Neurologic Events Following Axicabtagene Ciloleucel Administration(First infusion date of axicabtagene ciloleucel up to 24 months)
- Rates of Hospitalization After Axicabtagene Ciloleucel Infusion as Measured by Proportion of Hospitalized Participants Within 72 hours(First infusion date of axicabtagene ciloleucel up to 72 hours)
- Event Free Survival (EFS) as Assessed by Investigator Assessment(Up to 24 months)
- Peak Serum Levels of Homeostatic/Proliferative Cytokines: Interleukin (IL)-2, IL-7, and IL-15(Up to 24 months)
- Peak Serum Levels of Immune Effector Molecules: Granzyme A, Granzyme B, and Perforin(Up to 24 months)